Life at high altitudes forced ancient Tibetans to undergo
the fastest evolution ever seen in humans, according to a new study.

The most
rapid genetic change showed up in the EPAS1 gene, which helps regulate the body's
response to a low-oxygen environment. One version, called an allele, of the
EPAS1 gene changed in frequency from showing up in 9 percent of the Han Chinese
to 87 percent of Tibetans.

Such genetic changes suggest Tibetan ancestors split off
from the Han Chinese population about 2,750 years ago, researchers say. But
only those most evolutionarily suited for life at high altitudes survived when
they moved to the Tibetan Plateau.

"It took only a few hundred generations to change the
allele frequency, which can only happen if a lot of people have died,"
said Rasmus Nielsen, an evolutionary biologist at the University of California
at Berkeley. "In that sense, it must have had a strong effect on
fitness."

The Tibetan example of human evolution beats the previous
record holders in northern Europe, who evolved
lactose tolerance to digest the milk sugar lactose over the course of about
7,500 years.

Exactly how the EPAS1 allele helps humans adapt to oxygen
deprivation remains unknown. But the study suggests that most Han Chinese who
could not adapt to high-altitude environments did not do well in passing on
their genes.

From lowlands to mountains

Modern Tibetans have evolved to survive
the thin air (molecules of air become less tightly packed with altitude) without
making more red blood cells and hemoglobin, which is the protein that helps
carry oxygen in the blood.

By contrast, a lowlander would eventually see his or her body
compensate for the lack of oxygen by developing more red blood cells and
hemoglobin. That helps them deal with 40-percent lower oxygen levels compared with
sea level at elevations above 13,000 feet (3,962 meters).

"If we go to high altitude, we produce more hemoglobin,
but there's a cost to that," Nielsen told LiveScience. "Tibetans can
perform even better without the extra hemoglobin."

Too much hemoglobin can lead to chronic altitude sickness,
which involves thick and viscous blood. Lowlanders still end up tiring more
easily, developing headaches, having babies with lower birth weights and also
suffering higher infant mortality rates.

Nielsen and his colleagues in Europe and China focused on
tracing the evolutionary lineage of Tibetans, rather than starting with the
physiological changes that have made modern Tibetans so well-adapted to high
altitudes.

"Usually you'd take a lot of Tibetans who respond well
to oxygen deprivation and those who don't, and try to find a genetic
difference," Nielsen explained. "We did it the other way
around."

Counting the differences

The study sequenced 92 percent of the genomes of 50
non-related Tibetans living in two villages within the Tibet Autonomous Region
of China, as well as 40 Han Chinese from Beijing. The Tibetan villages were located
at elevations of 14,100 feet (4,300 meters) and 15,100 feet (4,600 meters).

The data came from the Beijing Genomics Institute (BGI) in
Shenzhen, which Nielsen described as the biggest sequencing center in the world
and capable of beating any Western counterparts.

Results revealed about 30 genes with mutations that had
become more common in Tibetans than in Han Chinese. Nearly half of those related
to how the body uses oxygen.

The most dramatic example of change came from a mutation carried
by one of the EPAS1 alleles. Tibetans with two mutated alleles – one from each
parent – had significantly lower hemoglobin concentrations and could still do
well at high altitudes.

But researchers could not say for sure whether the Tibetans
had evolved away from the Han Chinese or vice versa. They needed a third group
for comparison.

That group came in the form of 200 Danes, whose genomes had
almost zero percent of the EPAS1 allele thought to be adaptive for high
altitudes. The data combined with simulations to suggest the Tibetans had
undergone major
genetic changes.

Tracing lineage

Questions remain about not only the physiological
adaptations that make Tibetans fit for high-altitude living, but also about the
Tibetan ancestors and their origin.

The genetic analysis suggests the larger group of Tibetans
that moved to the Tibetan
Plateau some 2,750 years ago eventually shrank, while the smaller group
that moved to the lower elevations expanded greatly into the modern-day Han Chinese
population.

Historical evidence shows that people have lived on the
Tibetan Plateau for longer than 3,000 years, Nielsen noted. He and his
colleagues speculate the Tibetans either merged with the people already living
on the plateau, or replaced them.

Either way, Nielsen said the study has no relevance for the
ongoing debate over whether Tibet belongs as part of China. Ethnic groups
define themselves by culture and history, he added.

"I'm from Denmark and probably genetically
indistinguishable from someone from Sweden, but doesn't mean they're the same
country," Nielsen said. "I'd argue that genetics is irrelevant to
Tibetan self-determination."

Jeremy Hsu

Jeremy has written for publications such as Popular Science, Scientific American Mind and Reader's Digest Asia. He obtained his masters degree in science journalism from New York University, and completed his undergraduate education in the history and sociology of science at the University of Pennsylvania.